[Federal Register Volume 77, Number 143 (Wednesday, July 25, 2012)]
[Notices]
[Pages 43601-43603]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-18054]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

FOR FURTHER INFORMATION CONTACT: Licensing information and copies of 
the U.S. patent applications listed below may be obtained by writing to 
the indicated licensing contact at the Office of Technology Transfer, 
National Institutes of Health, 6011 Executive Boulevard, Suite 325, 
Rockville, Maryland 20852-3804; telephone: 301-496-7057; fax: 301-402-
0220. A signed Confidential Disclosure Agreement will be required to 
receive copies of the patent applications.

Novel Analogues of the Asthma Drug Fenoterol as Liver and Brain Cancer 
Therapeutic Agents

    Description of Technology: Available for licensing are specific 
fenoterol analogues, such as MNF, that inhibit the growth of various 
types of cancers, including brain, liver, colon, and lung tumors. MNF 
acts as an agonist of the

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GPRSS cannabinoid (CB) receptor and, as such, represents one of the 
first potential drugs directed at this target. MNF crosses the blood 
brain barrier and initial toxicity studies indicate that it has few 
off-target effects. These new analogues can be used to treat CB 
receptor related disorders and diseases, and in particular GRPSS-
related disorders and diseases, including brain and liver cancers for 
which there are no current effective treatments.
    Potential Commercial Applications:
     A new class of compounds that can be used to treat 
cannabinoid receptor related disorders and diseases.
     Treatments for liver, brain, colon, and lung cancers.
    Competitive Advantages:
     Able to cross the blood:brain barrier.
     Few side-effects.
     Broad range of therapeutic activity.
     Can be formulated for oral administration.
    Development Stage:
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Irving Wainer, Michel Bernier, Rajib Paul (all of NIA).
    Publications:
    1. Paul RK, et al. Cannabinoid receptor activation correlates with 
the pro-apoptotic action of the beta2-adrenergic agonist (R,R')-4'-
methoxy-1-naphthylfenoterol. J Pharmacol Exp Ther., in press.
    2. Paul RK, et al. Negative regulation of GPR-55-mediated ligand 
uptake and cellular motility by (R,R')-4'-methoxy-1-napthylfenoterol. 
Br J Pharmacol., in preparation.
    3. Paul RK, et al. The role of GPR55 and apoptotic signalling 
pathways in (R,R')-4'-methoxy-1-naphthyfenoterol. Cancer Res., in 
preparation.
    Intellectual Property: HHS Reference No. E-139-2012/0--U.S. 
Provisional Application No. 61/651,961 filed 25 May 2012.
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunities: The IRP/NIA/LCI is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
(R,R')-4'-methoxy-1-naphthylfenoterol for the treatment of brain, liver 
and colon carcinomas. For collaboration opportunities, please contact 
Nicole Guyton, Ph.D. at [email protected].

High-Affinity Mouse Monoclonal Antibodies to Glypican-3 (GPC3) for 
Research Use

    Description of Technology: Liver cancer is the fifth most common 
cancer in the world, with hepatocellular cancer (HCC) representing the 
preponderance of these liver cancers. As with many cancers, positive 
prognosis for a patient diagnosed with HCC correlates with the early 
detection of the disease. Unfortunately, HCC is usually detected at a 
late stage in its development, leading to poor prognosis for most 
patients. As a result, there is great interest and value in developing 
new agents which can detect the presence of HCC in a patient at an 
early stage.
    Glypican-3 (GPC3) is a cell surface heparan sulfate glycoprotein 
that is expressed on the vast majority of HCC cells. The correlation 
between GPC3 expression and HCC makes GPC3 an attractive candidate for 
studying the disease progression and treatment of HCC. The presence, 
progression and treatment of this disease can potentially be monitored 
by tracking the level of expression of GPC3 on cells. This can be 
accomplished using monoclonal antibodies which recognize only GPC3, 
particularly the cell surface domain of the protein. This invention 
concerns the generation of several monoclonal antibodies that are 
specific for the cell surface domain of GPC3 (YP6, YP7, YP8, YP9 and 
YP9.1), and which can be used as research reagents for studying the 
role of GPC3 in HCC.
    Potential Commercial Applications: Antibodies for use as research 
materials, including:
     Detection of cells that express GPC3 for monitoring HCC 
disease progression and treatment.
     Immunostaining for tumor imaging.
     ELISA and immunohistochemistry applications.
     Any other antibody-related research use, including 
immunoprecipitation, western blot analysis, etc.
    Competitive Advantages:
     Higher binding affinity (subnanomolar levels) than 
commercially available GPC3 antibodies such as 1G12.
     Recognition of cells with low levels of GPC3 expression.
     Able to bind to wild-type GPC3 (conjugated to heparan 
sulfate) better than the GPC3 core protein (lacking heparan sulfate).
    Development Stage:
     Early-stage.
     In vitro data available.
    Inventors: Mitchell Ho et al. (NCI).
    Publications:
    1. Ho M, Kim H. Glypican-3: a new target for cancer immunotherapy. 
Eur J Cancer. 2011 Feb; 47(3):333-338. [PMID 21112773]
    2. Ho M. Advances in liver cancer antibody therapies: a focus on 
glypican-3 and mesothelin. BioDrugs. 2011 Oct 1; 25(5):275-284. [PMID 
21942912]
    Intellectual Property: HHS Reference No. E-136-2012/0--U.S. 
Provisional Application No. 61/654,232 filed 01 Jun 2012.
    Related Technology: HHS Reference No. E-130-2011/0 -- U.S. 
Provisional Application No. 61/477,020 filed 19 Apr 2011; PCT 
Application No. PCT/US2012/034186 filed 19 Apr 2012.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate or commercialize 
cancer diagnostics, isolation of circulating tumor cells, humanization 
and/or immunoconjugates. For collaboration opportunities, please 
contact John Hewes, Ph.D. at [email protected].

Self-Assembled Ferritin Nanoparticles Expressing Hemagglutinin as an 
Influenza Vaccine

    Description of Technology: NIH inventors at the Vaccine Research 
Center have developed a novel influenza virus hemagglutinin (HA)-
ferritin nanoparticle influenza vaccine that is easily manufactured, 
potent, and elicits broadly neutralizing influenza antibodies against 
multiple strains of influenza. This novel influenza nanoparticle 
vaccine elicited two types of broadly neutralizing, cross-protective 
antibodies, one directed to the highly conserved HA stem and a second 
proximal to the conserved receptor binding site (RBS) of the viral HA, 
providing a new platform for universal and seasonal influenza. In 
addition, HA-ferritin nanoparticles can be easily produced from simple 
expression vectors and without the production of infectious virus in 
eggs, and will facilitate influenza preparedness in the face of 
emerging epidemics.
    This technology exploits ferritin, a ubiquitous iron storage 
protein, that self-assembles into spherical nanoparticles and could 
serve as a scaffold to express a heterologous protein, such as 
influenza HA, so it mimics a physiologically relevant trimeric viral 
spike. Immunization with the HA-ferritin nanoparticle elicited 
neutralizing antibody titers that were >10-fold higher than a matched 
inactivated vaccine. The immune sera raised by HA-ferritin 
nanoparticles

[[Page 43603]]

expressing a 1999 HA neutralized seasonal H1N1 viruses from 1934 to 
2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. 
This extended neutralization coverage is partially explained by the 
presence of both type of antibodies, antibodies directed to the 
conserved HA stem and against the RBS region. Finally, this ferritin 
nanoparticle vaccine platform has significant advantages in the ability 
to utilize specific multimerized spikes and it may be applicable to 
other viral proteins.
    Potential Commercial Applications: The ferritin nanoparticles as a 
vaccine platform can be used to deliver vaccines, such as influenza 
vaccines, with enhanced magnitude and breadth of the neutralizing 
antibody responses. This vaccine platform may be applicable to other 
viral proteins.
    Competitive Advantages:
     Forms an octahedron consisting of 24 subunits, allowing 
for greatly increased presentation of heterologous protein on the 
ferritin nanoparticles surface, compared to other vaccine platforms.
     In vivo data in multiple animal models demonstrated 
induction of broader and more potent antibody responses.
     Vaccine stimulated broadly neutralizing antibodies against 
the highly conserved epitope on the HA stem region and against the RBS, 
thus targeting two independent sites of vulnerability on HA.
     Multivalent influenza HA ferritin vaccines have been 
tested in animal models.
     Ferritin is extremely stable to temperature ranges, pH, 
detergent and other factors.
     Easily manufactured, will facilitate influenza 
preparedness in the face of emerging epidemics.
    Development Status:
     Preclinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Gary Nabel, Masaru Kanekiyo, Jeffrey C. Boyington, 
Patrick McTamney (all of NIAID).
    Publication: Kanekiyo M, et al. A Self-Assembling Influenza 
Nanoparticle Vaccine Elicits Two Types of Broadly Neutralizing and 
Cross-protective Antibodies. Manuscript submitted.
    Intellectual Property:
     HHS Reference No. E-293-2011/0 -- U.S. Provisional 
Application No. 61/538,663 filed 23 Sep 2011.
     HHS Reference No. E-293-2011/1 -- U.S. Provisional 
Application No. 61/661,209 filed 18 Jun 2012.
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301-
435-4507; [email protected].

Salen-Manganese Compounds for Therapy of Viral Infections

    Description of Technology: Salen-manganese compounds are synthetic, 
stable, low toxicity, low cost agents that may provide protection from 
immune reaction-related oxidative cell damage associated with many 
illnesses. In particular, oxidative cell damage has been associated 
with many viral infections including influenza. This invention 
demonstrates that treating mice with salen-manganese compounds, after 
lethal pandemic influenza virus infection, significantly enhances 
survival. Salen-manganese treatment also reduces lung pathology and 
also improved cellular recovery and repair. Because oxidative damage is 
observed in many viral infections, administration of salen-manganese 
compounds may have therapeutic relevance to a wide range of viral 
infections, in addition influenza. Existing viral therapeutics merely 
target the infectious viral agent and not the damage caused by the 
immune system reaction related to infection. Because, salen-manganese 
treatments target the untapped therapeutic space of infection-induced, 
immune system-related pathology and have favorable safety and cost 
profiles, such therapies are ideal candidates for development.
    Potential Commercial Applications: Viral therapeutics.
    Competitive Advantages: Synthetic, stable, low toxicity, low cost, 
untapped therapeutic target space.
    Development Stage:
     Early-stage.
     Pre-clinical.
     In vivo data available (animal).
    Inventors: John Kash (NIAID), Jeffrey Taubenberger (NIAID), Rodney 
Levine (NHLBI), Susan Doctrow (Boston University).
    Publications:
    1. Doctrow SR, et al. Salen Manganese Complexes: Multifunctional 
Catalytic Antioxidants Protective in Models for Neurodegenerative 
Diseases of Aging. In: Medicinal Inorganic Chemistry, ACS Symposium 
Series, Vol. 903, Chapter 18, pp 319-347; August 25, 2005. [DOI: 
10.1021/bk-2005-0903.ch018.]
    2. Schwarz KB. Oxidative stress during viral infection: a review. 
Free Radic Biol Med. 1996; 21(5):641-9. [PMID 8891667]
    Intellectual Property: HHS Reference No. E-281-2011/0--U.S. 
Provisional Application No. 61/558,137 filed 10 Nov 2011.
    Licensing Contact: Tedd Fenn, J.D.; 301-435-5031; 
[email protected].
    Collaborative Research Opportunity: The NIAID Laboratory of 
Infectious Diseases, Viral Pathogenesis and Evolution Section, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
this technology. For collaboration opportunities, please contact 
Maryann Puglielli at 301-594-6656.

    Dated: July 18, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-18054 Filed 7-24-12; 8:45 am]
BILLING CODE 4140-01-P